Molecular Modeling of Nucleic Acid Structure: Setup and Analysis

Abstract

The last in a set of units by these authors, this unit addresses some important remaining questions about molecular modeling of nucleic acids. It describes how to choose an appropriate molecular mechanics force field; how to set up and equilibrate the system for accurate simulation of a nucleic acid in an explicit solvent by molecular dynamics or Monte Carlo simulation; and provides some information about how to analyze molecular dynamics trajectories. ISSUES WITH SIMULATING NUCLEIC ACIDSFrom the information presented in previous units (UNITS 7.5, 7.8 & 7.9), one should have a reasonable understanding of the various trade-offs that are necessary to model nucleic acid structures. For instance, when choosing an energy representation and a means to sample relevant conformations, there is a tradeoff between detail, sampling, and computational cost. Although the discussions thus far have presented basic means for modeling nucleic acids, some important details have not been sufficiently addressed. Reasonable decisions that remain for the prospective modeler to address are: (1) which empirical molecular mechanical force field is appropriate; (2) if one wants to run an accurate simulation of a nucleic acid in an explicit solvent, how does one set up and equilibrate the system; (3) how long should the production time of the simulation be in order to see convergence in properties of interest; and (4) how does one analyze molecular dynamics trajectories? This unit provides the answers to some of these questions and outlines a protocol for accurate simulation of nucleic acids.

In silico analyses on the comparative sensing of SARS‐CoV‐2 mRNA by the intracellular TLRs of humans

“…In silico molecular docking between receptor (TLR) and ligand (RNA) is not sufficient to conclude on the nature of the complex, further analysis, namely, MD simulation is desirable to validate the structural stability of that complex. GROningen MAchine for Chemical Simulations (GROMACS) is the foretmost platform for the MD simulations as it possesses the ability to employ different force fields to generate simulation data not only of proteins complexes but also complexes of DNA–protein and RNA–protein 28 …”

“…GROningen MAchine for Chemical Simulations (GROMACS) is the foretmost platform for the MD simulations as it possesses the ability to employ different force fields to generate simulation data not only of proteins complexes but also complexes of DNA-protein and RNA-protein. 28 In this study, the Chemistry at Harvard Macromolecular Mechanics (CHARMM) force field was accessed initially to generate necessary input files for MD simulation. [29][30][31] The solution builder approach under CHARMM-GUI web tool was first employed to add the water box (TIP3 216) and then neutralize the atoms to solvate the system.…”

In silicoanalyses on the comparative sensing of SARS-CoV-2 mRNA by intracellular TLRs of human

“…GROningen MAchine for Chemical Simulations (GROMACS) is the utmost platform for the MD simulations as it possesses ability to employ different force fields to generate simulation data not only of proteins complexes but also complexes of DNA-protein and RNA-protein. 28…”

“…GROningen MAchine for Chemical Simulations (GROMACS) is the utmost platform for the MD simulations as it possesses ability to employ different force fields to generate simulation data not only of proteins complexes but also complexes of DNA-protein and RNA-protein. 28 In this work, Chemistry at Harvard Macromolecular Mechanics (CHARMM) force field was accessed initially to generate necessary input files for MD simulation. [29][30][31] Solution builder approach under CHARMM-GUI web tool was first add water box (TIP3 216) and then neutralizing atoms to solvate the system.…”

Deformability Calculation for Estimation of the Relative Stability of Chemically Modified RNA Duplexes

“…As mentioned in the previous section, general protocols for MD simulations have been reported (UNIT 7.10; Galindo-Murillo et al, 2014). In addition, detailed tutorials are provided on the AMBER Web site (Tutorial B1).…”